Amebiasis, a significant cause of morbidity and mortality throughout the world, is caused by invasion of the colonic mucosa by the cytolytic protozoan parasite. Entamoeba histolytica. We have identified the neurohumoral substances, Serotonin, Substance P and neurotensin in extracts of amebae. The goal of this application is to identify the neurohumoral substances and their role in the diarrheal syndrome seen in amebiasis. We have demonstrated that amebic lysate decreases Na and Cl transport in the animal intestine in vitro. This effect is partially inhibited by specific anti-serotonin antibody suggesting that serotonin plays a role but is not totally responsible for the amebiclysate effect on active electrolyte transport. We propose to more fully characterize the effect of amebic lysates on active intestinal electrolyte transport using the modified Ussing chamber - voltage clamp technique. We will study the effect of amebic lysates on ion fluxes, intestinal cyclic nucleotide content and cross-desensitization to other neurohumoral substances. We will attempt to define the role of prostaglandins in the effect on electrolyte transport by attempting to block the effect with agents which interfere with arachidonic acid metabolism including cyclo-oxygenase and lipoxygenase inhibitors. We will also attempt to inhibit the effects of the neurohumoral agents with antibody to amebal extracts and specifically to the neurohumoral substances found to be present in amebic lysates.